Burned patients have an aberrant response to neuromuscular (NM) relaxants. They can develop hyperkalemic cardiac arrest with the administration of the depolarizing NM relaxant, succinylcholine (SCh). In addition there is a 3 to 5 fold increase in the dose and plasma concentration requirement for nondepolarizing NM relaxants such as d-tubocurarine (dTc). Altered kinetics do not explain these effects. Similar responses occur following denervation, disuse atrophy, sepsis, and immune-suppressed states. In denervation and disuse atrophy the aberrant responses are related to increases in acetylcholine receptors (AChR) or to decreases in acetylcholinesterase enzyme (AChE) activity. Physico-chemical and functional changes and causes for these changes occuring at the NM junction following burns are unknown. Two hypotheses will be tested. First, that the altered response to NM relaxants is due to an increase in AChR at the NM junction. The second, that the aberrant response is due to depressed AChE activity which results in decreased breakdown leading to increased levels of acetylcholine. Thus, in the rat burn model, studies of SCh-K+ release and dTc hyposensitivity will be correlated to changes in AChR number and AChE activity. 125I alpha-bungarotoxin will be used to quantitate AChR. By studying changes in AChR and AChE both in the gastrocnemius and diaphragm, the local and systemic effects respectively of burn on skeletal muscle will be discriminated. The putative factors that might contribute to these changes will also be studied, including the chronic effects of malnutrition, immunosuppression, antibiotic therapy and sepsis. Thus, in the non-burned rat, by the chronic infliction of antibiotic therapy (streptomycin), malnutrition, immune suppression (azothiaprine) and non-lethal bactremia the contribution of each to NM changes will be examined. Functional changes will be assessed by monitoring peak developed tension and fatigue characteristics. These studies will provide basic information on: 1) burn induced physico-chemical changes at the NM junction; and 2) surgical factors controlling AChR number and AChE activity at the NM junction and the functional significance of these changes. Finally the studies should provide some insight into the etiology of the clinically observed peripheral neuropathic and myopathic complications. Thus, in the long term these studies will provide a rational basis for pharmacologic manipulation to prevent or treat these complications accompanying burn injury.